tbuckley/cabot-search huggingface dataset:
Do future innovations in development influence oncologists’ treatment recommendations today? A survey of U.S. oncologists.
Authors: Meng Li, Zizi Elsisi, William Bruce Wong, Stacey Kowal, David L Veenstra, Louis P. Garrison
Journal: Journal of Clinical Oncology (2023)

e24004 Background: Survival benefit from current anticancer treatments, even if modest, improves a patient’s chances of accessing and benefiting from future innovations currently in clinical development. No studies to date have evaluated the potential impact of future innovations on oncologists’ treatment recommendations. Methods: We conducted a national survey of medical and hematologic oncologists (n = 200) on how expectations about future innovations may influence their treatment recommendations today. The survey described a hypothetical patient with metastatic cancer, whose median overall survival (OS) was approximately 6 months with most dying within 2 years. We presented four alternative hypothetical scenarios of new innovations in the clinical development pipeline with varying (a) expected efficacy—“modest” (improvement in median OS of 2 months} or “breakthrough” (improvement in median OS of 6 months) and (b) time of arrival (in 6 months or 1 year). We asked the oncologists about the likelihood (using a 5-point Likert scale) (1) that they would discuss these new innovations with the hypothetical metastatic patient, and (2) that these new innovations would influence their recommended treatment for the patient today. We descriptively summarized percentages of oncologists who responded “likely” or “very likely” and examined their associations (using multivariate logistic regression) with the expected efficacy and time of arrival of future innovations as well as the characteristics of oncologists and their practice. Results: When future innovations were expected to have modest efficacy and arrive in 6 months, 61% of oncologists reported that they would be likely or very likely discuss them with their patients, and 52% reported new innovations would influence their treatment recommendations today. With modest efficacy and time of arrival in 1 year, percentages dropped to 49% and 41%, respectively. With breakthrough efficacy and arrival in 6 months, 76% would discuss and 68% would consider new innovations. With breakthrough efficacy and arrival in 1 year, percentages dropped to 62% and 55%, respectively. Greater expected efficacy and shorter time to arrival were associated with a significantly greater likelihood of discussing a future innovations with patients across oncologist and practice characteristics (adjusted odds ratios: breakthrough vs. modest = 1.75; 6 month vs. 1 year = 1.72). Conclusions: Future treatment innovations in clinical development are relevant for decision-making today even when anticipated time to arrival is two times the current median OS. results indicate that it is important to include future innovations in shared decision-making in addition to the benefit-risk balance of current treatments.
Real-world outcomes with novel therapies in R/R DLBCL.
Authors: Jennifer Leigh Crombie, Monika P. Jun, Tongsheng Wang, Alex Mutebi, Anthony Wang, Anindit Chibber, Rajesh Kamalakar, Jon Ukropec, Julie Blædel, Anupama Kalsekar
Journal: Journal of Clinical Oncology (2023)

7552 Background: Outcomes have historically been poor for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Despite an increase in approved R/R DLBCL treatment options, clinical outcomes of these therapies remain less certain. Novel treatments for R/R DLBCL patients include chimeric antigen receptor T-cell (CAR T) therapy, polatuzumab vedotin plus bendamustine and rituximab (pola-BR), tafasitamab plus lenalidomide (tafa-len), loncastuximab (lonca), and selinexor. The objective of this study was to examine real-world outcomes of these novel therapies. Methods: US patient data from the COTA electronic health records database (2010–2021) were used for this retrospective study. Patients had a diagnosis of DLBCL after 1/1/2010, with ≥1 prior line of systemic antineoplastic therapy (including an anti-CD20 antibody), and treatment with any of these novel therapies. Patients receiving variations of pola-BR or tafa-len regimens were included. Outcomes included overall response rate (ORR), complete response (CR) rate, median progression-free survival (mPFS), and median overall survival (mOS). Outcomes were also analyzed for those treated with any novel therapy following prior CAR T exposure. Results: A total of 175 R/R DLBCL patients were included (median age 63 y, 60.6% male, median of 2 prior therapies); 29.1% had an international prognostic index score ≥3, 61.7% had stage III/IV disease, and 65.7% had primary refractory disease. A total of 73, 69, and 27 patients were treated with CAR T, pola-BR, and tafa-len regimens, respectively. Only 6 patients were treated with lonca and no patients received selinexor. Among 169 patients treated in the 2L+ setting with tafa-len, pola-BR, and CAR T, the CR rate was 11.1%, 18.8%, and 52.1%, respectively (Table). A total of 112 patients were treated in the 3L+ setting with CR rate of 10.0%, 13.5%, and 41.8%, for tafa-len, pola-BR, and CAR T, respectively. Outcomes in the 18% of patients treated with any novel agent following CAR T exposure were ORR of 19.1%, CR of 4.8%, and mPFS and mOS of 1.4 mo and 2.3 mo, respectively. Conclusions: Outcomes of pola-BR and tafa-len regimens in the 2L+ and 3L+ R/R DLBCL setting remain suboptimal, with worse outcomes as patients advance through lines of therapy. Outcomes are particularly poor when these agents are used following CAR T therapy. [Table: see text]
Efficacy of combination lurbinectedin (LURBI) + doxorubicin (DOX) from the phase 1B soft-tissue sarcoma (STS) lead-in to a randomized phase 2 trial in leiomyosarcoma (LMS).
Authors: Gregory Michael Cote, Candace L. Haddox, Edwin Choy, Priscilla Merriam, Emanuele Mazzola, Andrew J. Wagner, Brittany L. Siontis, Steven Attia, Mahesh Seetharam, George D. Demetri, Suzanne George
Journal: Journal of Clinical Oncology (2023)

11507 Background: Single agent or combination chemotherapy, typically Dox- or gemcitabine-based, are standard 1st- and 2nd-line therapies in patients (pts) with metastatic LMS; however, objective response rates (ORR), progression-free, and overall survival (PFS/OS) remain inadequate. Lurbi (PharmaMar S.A. / Jazz Pharmaceuticals) binds to DNA inhibiting transcription and inducing double strand breaks leading to apoptosis and delaying S/G2 progression. In a prior pilot study, we showed Lurbi+Dox is well-tolerated, with signs of activity, particularly in LMS. We designed this phase 1b to optimize dosing to lead into a randomized (1:1) phase 2 trial of Dox+/-Lurbi in anthracycline-naïve LMS. Herein we provide updated efficacy and tolerability data for this Phase 1b cohort. Methods: Pts &gt; 18 yrs with locally advanced/metastatic, unresectable non-GIST STS (Phase 1b only) w/o prior anthracycline or Lurbi/trabectedin, ECOG PS &lt; 3, RECIST 1.1 measurable, and normal organ function were eligible. The phase 1b followed a 3+3 design. Dosing included fixed Lurbi (3.2 mg/m 2 d1) with two Dox dose levels (DL; DL1: 25 mg/m 2 d1; DL2 25 mg/m 2 d1+8). All pts received GCSF prophylaxis. Tumor assessments were every 2 cycles. DL1 was chosen as RP2D and the phase 2 trial began accrual in Aug 2022 aiming to enroll 50 LMS pts randomized 1:1 (stratified by uterine LMS [uLMS]] v. other LMS) with PFS as primary endpoint. Pts progressing on Dox are allowed to cross to Lurbi monotherapy. Results: 10 patients were enrolled in Phase 1b. Histologies included 5 LMS (4 uLMS) and 1 each of myxofibrosarcoma (myxFS), undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), endometrial stromal sarcoma (ESS), and solitary fibrous tumor (SFT). With a median follow-up of 344 days, 5/10 pts remain on treatment with median PFS of 357 days (95%CI 175-ND). 6 pts demonstrated partial response (PR; 5 confirmed), 3 with stable disease (SD), and 1 with progressive disease (PD, Table). Median time to PR was 81 days (range 46-207). Duration of response was over 132 days in all responders with 3 still on treatment. Treatment-related AEs were typical for Dox/Lurbi, including nausea, fatigue, and reversible LFT elevations/cytopenias. Updated safety and response data will be provided at the time of the meeting. Conclusions: Lurbi+Dox is well-tolerated with efficacy in STS including 6/10 pts achieving PR, 9/10 pts staying on treatment for &gt;120d, and 6/10 pts &gt;200d. The randomized phase 2 study is currently enrolling. Clinical trial information: NCT05099666 . [Table: see text]
Outcomes of intravenous and subcutaneous cladribine administration in patients with hairy cell leukemia: A systematic review and meta-analysis.
Authors: Jawad Basit, Zaofashan Zaheer, Muhammad Hammad Khan, Maurish Fatima, Sobaan Taj, Usman Ali Akbar, Mohammad Ebad Ur Rehman, Sajeel Saeed, Sindhu Vikash, Nithya Ramesh, Asna Shahab, Muhammad Shahid, Aqsa Komel, Umer Irshad, Shehroze Tabassum, Aroma Naeem
Journal: Journal of Clinical Oncology (2023)

e19546 Background: Hairy cell leukaemia (HCL) is a rare, chronic B cell cancer that involves the bone marrow, peripheral blood, and spleen. Cladribine (2CdA) monotherapy is used as a first line treatment for HCL. 2CdA can be administered intravenously (IV) or subcutaneously (SC). The aim of our study is to compare the safety and efficacy of these two routes of administration of 2CdA as a first line treatment of HCL. Methods: We conducted a systematic literature search across multiple databases and Google up to February 2023. We included studies that reported outcomes for either intravenous (IV) or subcutaneous (SC) cladribine (2CdA) therapy, as well as those that directly compared the two routes. Our primary efficacy outcomes were overall response rate (ORR) and complete response rate (CRR), and our primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random effects model and conducted subgroup analysis for HCL type (classical vs classic and variant both). We calculated odds ratios (ORs) for studies involving a head-to-head comparison between the two routes and used the Higgins I2 statistic to assess heterogeneity. Results: We identified a total of 25 studies (15 trials, 10 cohorts) with a patient population of 2669. The median age of the patients was 53.5 years. The pooled ORR and CRR for IV and SC 2CdA therapy were 96%, 82%, 88% and 67% respectively. The incidence of neutropenia (82% vs 61%) and infections (13% vs 16%) was greater for SC 2CdA than IV 2CdA. Five studies provided a direct comparison between SC and IV routes but three were excluded from the analysis due to unavailability of desired outcomes. Studies involving a direct comparison between the 2 routes of administration showed that the odds of achieving CRR were 86.6% greater with IV than SC 2CdA but these results were not significant. The proportion of adverse events was comparable for IV and SC routes. Subgroup analysis for HCL type did not resolve heterogeneity for ORR and CRR. It did, however, result in greater ORR for classic (92%) and mixed (92%) HCL treated with SC 2CdA. Conclusions: Compared to SC 2CdA, IV 2CdA is safer and more effective as a first-line treatment of HCL. However, future high-power randomized control trials that directly compare IV and SC routes are needed to confirm this evidence. [Table: see text]
COVID-19 infection in patients on anti-CD20 monoclonal antibodies: Changes in clinical outcomes and management over time.
Authors: Mohammad Ali, Hafez M Abdullah, Mamoon Ahmed, Hammad Chaudhry, Dawlat Khan, Fouad Khalil, David Wachira, Jonathan Bleeker
Journal: Journal of Clinical Oncology (2023)

e19542 Background: As the COVID-19 pandemic progressed, survival of patients in the general population with COVID-19 improved over time. It is less clear based on current data whether patients on anti-CD20 therapy experienced similar improvement in outcomes over time. Methods: We performed a retrospective study of all patients aged ≥ 18 years diagnosed with COVID-19 while receiving anti-CD20 therapy for hematologic malignancy and/or rheumatologic indications at our center from January 2020-January 2022. Our primary endpoint was median overall survival (OS) and clinical outcomes stratified by date of diagnosis (“early cohort” = 03/01/20 to 12/31/20, “later cohort” = 01/01/21 to 10/15/21, and “latest cohort” = 10/16/21 to 01/16/22”). Secondary endpoints were to describe changes in the management of patients receiving anti-CD20 agents as the pandemic progressed and to assess independent predictors of OS in this population. Results: The median OS of 186 patients in the entire group was 13 months and the case fatality rate (CFR) was 23%. The CFR of admitted patients was 84%, whereas it was 16% for those who were not admitted. To examine trends over time, we compared 71 patients in the early cohort to 69 in the later cohort, and 42 patients in the latest cohort. The median OS of patients in the early cohort was 18 months (0.1-27) compared to 9 months (0-22) in the later cohort, and 8 months (0-20) in the latest cohort (P = 0.1884). The proportion of patients who received steroids was relatively consistent as the pandemic progressed with 45% in the early vs. 41% in the latest cohort. Fewer patients received remdesivir (31% for early cohort vs 21% for latest cohort) and convalescent plasma (13% for early cohort vs 2% for latest cohort) over time. The only baseline or treatment characteristics associated with adverse outcomes were receipt of steroids and anticoagulation, both of which were associated with an increased risk of death ((HR = 5.5, p = 0.002) and (HR = 2, p = 0.043 respectively)). Conclusions: Patients receiving monoclonal anti-CD20 antibody therapy had worse clinical outcomes than previously reported outcomes for the general population. OS did not significantly improve as the pandemic progressed; the phase of the pandemic with the shortest median OS was from 01/01/21 to 10/15/21 during the Delta SARS-COV-2 wave. Our data demonstrates an increased risk of death in patients on monoclonal anti-CD20 who experienced a COVID-19 infection and were treated with steroids, consistent with other reports.
Self-reported sleep difficulties and association with cognitive function in pediatric cancer survivors.
Authors: Pete Stavinoha, Grace Waterman, Bridgette Carroll, Alice Ann Holland, Marsha N Gragert, Grace Yang, Jinbing Bai, Maria Chang Swartz
Journal: Journal of Clinical Oncology (2023)

10065 Background: Preventing and ameliorating cognitive impairment following treatment for pediatric cancer remains a persistent challenge, with recent literature examining lifestyle factors as possible targets for intervention. An association between sleep and cognitive impairment has been identified in adult cancer patients and survivors, yet information is limited for pediatrics. Thus, the primary goal of our retrospective study was to explore self-reported sleep difficulties in pediatric patients and survivors with mixed cancers. A secondary aim was to explore the impact sleep problems on specific cognitive functions. Methods: Children and adolescents who completed neuropsychological assessments at two large pediatric cancer centers (N = 298) were identified via medical record review. In addition to demographic data, clinically collected cognitive tests included Wechsler Working Memory (WMI), Processing Speed (PSI), and General Ability (GAI) indices. Objective attention measures included Conners Continuous Performance Test (versions II and 3) Omissions (O), Commissions (C), and Reaction Time (RT). Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) were captured using pediatric self-report PROMIS scales. PROMIS cut points were used to categorize sleep issues within the study population and PROMIS scores were compared to reference population means. Multiple linear regression was used to identify relationships between cognitive domains and sleep factors. Common cancer-related clinical and demographic characteristics were controlled as covariates. Results: 21.5% of patients reported severe SD, while 12.8%, 15.9% and 49.7% reported moderate, mild, and within normal limits (WNL) SD, respectively. For SRI, 13.3% reported severe SRI, while 20.0%, 15.9% and 50.8% reported moderate, mild and WNL SRI, respectively. Mean SD and SRI were higher than in the reference populations (p = 0.000 for both measures). Pearson correlation results suggested a moderate relationship between SD and SRI (r = 0.489, p = 0.000). After controlling for covariates, multiple linear regressions indicated significant relationships between SD and GAI (p = 0.006), SD and O (p = 0.018), and SRI and WM (p = 0.006). Conclusions: Results suggested that ~50% of our pediatric cancer patients and survivors reported SD and SRI. SD was correlated with SRI in our sample, and regression analysis indicates a significant relationship between sleep problems and O, WM, and GAI in our sample. Findings from this retrospective study suggest a relationship between sleep problems and cognitive performance in pediatric cancer survivors. As a potentially modifiable factor to improve cognitive function in pediatric cancer survivors, sleep difficulties warrant more research to potentially guide interventions to better manage and improve cognitive function in this population.
Tumor microenvironment-mediated immune profiles and efficacy of platinum doublet chemotherapy plus ICIs stratified by DLL3 expression in small cell lung cancer.
Authors: Masayuki Shirasawa, Tatsuya Yoshida, Kouya Shiraishi, Shigehiro Yagishita, Yuji Matsumoto, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Katsuhiko Naoki, Takaaki Tsuchida, Ryuji Hamamoto, Noboru Yamamoto, Noriko Motoi, Takashi Kohno, Shun-ichi Watanabe, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2023)

8586 Background: Delta-like ligand 3 (DLL3) frequently expressed in small cell lung cancer (SCLC) and has been emerged as a therapeutic target. However, it remains unclear how DLL3 expression status affects tumor microenvironment (TME)-mediated immune profiles and clinical outcomes of platinum doublet chemotherapy plus ICIs in SCLC patients. Methods: We retrospectively reviewed post-surgical limited-stage (LS)-SCLC, and extensive-stage (ES)-SCLC patients treated with platinum and etoposide (PE) plus anti-PD-L1 antibody. In LS-SCLC cohort, the transcriptome and whole-exome sequencing (WES) analysis were performed to assess the immune profiles, mutation status and neoantigen status. In ES-SCLC cohort, the association between the efficacy of immunochemotherapy and DLL3 expression by transcriptome analysis were evaluated. Results: Fifty-nine and 17 patients were included in the LS- and ES-SCLC cohort, respectively. In LS-SCLC cohort (n = 59), WES analysis revealed that SCLC with DLL3 High had a significantly higher number of neoantigens (77 [95% confidence interval [CI] 65-113 ] vs. 48 [95% CI 17-58], p = 0.004), and a significantly higher rate of signature SBS4 associated with smoking (43% [95% CI 28-53] vs. 28% [95% CI 15-36], p = 0.02), although TMB did not differ according to DLL expression (6.6 mut/Mb [95% CI 5.3-9.6] vs. 6.5 mut/Mb [95% CI 5.2-9.9], p = 0.26). The transcriptome analysis in LS-SCLC cohort revealed that SCLC with DLL3 High tumors had significantly suppressed immune-related pathways (IFN-γ response, inflammatory response, and TNFα signaling via nfkb), and dendritic cells (DC) function (DC Differentiation, DC Antigen Processing and Presentation, DC Migration). Profiling tumor infiltrating immune cells with CIBERSORT showed that SCLC with DLL3 High had significantly lower proportions of T-cells, macrophages, and DCs compared with those with DLL3 low . These results suggested that DLL3 High tumors suppressed tumor immunity by inhibiting antigen-presenting function. In ES-SCLC cohort (n = 17), the PFS of PE plus anti-PD-L1 antibody in patients with DLL3 High was significantly worse than those in patients with DLL3 Low (4.1 months [95% CI, 2.0-6.3] vs. 7.4 months [95% CI, 2.5-12.3]; HR 3.78 [95% CI, 1.1-12.5], p = 0.03). Conclusions: SCLC with high DLL3 expression was characterized by resistance to immunochemotherapy due to suppressed tumor immunity, although those tumors had higher neoantigen loads.
Digital voice analysis as a measure of frailty and distress: A feasibility study (DIVAN).
Authors: Marcus Vetter, Simone Hemm, Cédric Schmid, Jan Gaertner
Journal: Journal of Clinical Oncology (2023)

TPS12139 Background: Assessing of frailty is essential not only in older patients with cancer, because frailty changes management of cancer therapy. Same is true for the routine assessment of distress to identify patient suffering and initiate adequate symptom control or psychosocial interventions. Here we present new potential method of frailty and distress assessment with digital voice analysis as a proof of concept trial. (NCT requested pending, DIVAN-1). Methods: Adult patients with the diagnosis of active incurable cancer can be enrolled into this study. Every participant will describe two to four images presented to him or her on a tablet computer in up to four sessions, and the patient`s voice will be recorded digitally. Baseline characteristics including cancer type, stage, therapy, G8 questionnaire and distress questionnaire (ESAS) will be collected at every session. Acoustic features like mean fundamental frequency (F0) and first few formants (F1, F2, etc.), jitter (variation in F0 from cycle to cycle), shimmer (variation in peak-to-peak amplitude), etc. will be explored digitally along with for example and voice strength (volume). Additionally, a vowel test will conducted and explored. Depending on the distribution of the data, the Pearson R correlation test or the Spearman’s R correlation test will be applied for each variable. The primary research question of this feasibility study is to identify quantitative parameters out of the audio signal to describe the changes in patient’s state in relation to frailty and distress. Trial enrolment has begun in December 2022 and 11 out of 100 patients have been included. Clinical trial information: NCT05783401 .